Mitogen activated protein kinases blockade improves lipopolysaccharide-induced ileal motor disturbances

Sergio Gonzalo1, Laura Grasa, Ligia Verónica Hernández

  • 1Department of Pharmacology and Physiology, Unit of Physiology, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.

Abstract

Insights

Lipopolysaccharide (LPS) reduces acetylcholine-induced ileum contractions. Mitogen-activated protein kinases (MAPKs), including p38, JNK, and ERK, are involved in this LPS effect in the ileum.

Area of Science:

  • Gastroenterology
  • Cellular and Molecular Physiology

Background:

  • Sepsis, often caused by lipopolysaccharide (LPS) from gram-negative bacteria, can impact the ileum.
  • LPS is a key endotoxin in sepsis pathogenesis.

Purpose of the Study:

  • To investigate the role of mitogen-activated protein kinases (MAPKs) in LPS-induced alterations of acetylcholine-stimulated rabbit ileum contractions.
  • To determine the localization of MAPKs within the ileum.

Main Methods:

  • Ileal contractility was assessed using an organ bath setup.
  • Immunohistochemistry was employed to localize MAPKs in ileal tissues.

Main Results:

  • LPS significantly decreased acetylcholine-induced ileum contractions.
  • Specific MAPK inhibitors (SB203580, SP600125, U0126) reversed the LPS-mediated reduction in contractions.
  • Phosphorylated p38 and ERK were found in myenteric plexus neurons, while phosphorylated p38 and JNK were identified in ileal smooth muscle cells.

Conclusions:

  • The study suggests that p38, JNK, and ERK MAPKs play a crucial role in the mechanism by which LPS affects the ileum.
  • These findings elucidate the cellular signaling pathways involved in LPS-induced ileal dysfunction.

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